Thymosins refer to a family of biochemically and functionally distinct proteins that were originally identified from the thymus, but which are now known to be present in many other tissues, and which have a variety of different physiological functions. More than 20 isoforms of beta-thymosin have been identified in different species, and among humans, three beta-thymosins have been identified, including thymosin beta-4, thymosin beta-10, and thymosin beta-15, all of which share significant amino acid sequence homology. Despite this homology, each of these thymosin beta proteins is a distinct gene product with different functions.
Thymosin beta-4, the most abundant of the beta-thymosins, is a highly conserved, water-soluble amino acid acidic polypeptide. The mammalian gene encoding thymosin beta-4 localizes to the X-chromosome. Human thymosin beta-4, X-linked, has 44 amino acids (msdkpdmaei ekfdksklkk tetqeknplp sketieqekq ages, SEQ ID NO:1), and escapes X-inactivation by being processed into a 43 amino acid peptide, with a molecular weight of 4.9 kDa, by removal of the first methionyl residue (Girardi, M., et al., Immunology 2003, 109: 1-7). Thymosin beta-4 is localized to both the cytoplasm and the nucleus of cells. Thymosin beta-4 is present in many tissues, and has multiple biological functions. It potently regulates actin polymerization, stimulates tissue remodeling, cell differentiation, and cell and tissue healing after injury, and is also involved in the expression of a number of inflammatory chemokines and cytokines.
The inventors have examined the mode of operation of retinol in human skin, and have made the discovery that retinol is a potent upregulator of thymosin beta-4. This surprising result lead to the search for additional agents that upregulate thymosin beta-4, that could act as potential alternatives or replacements for retinol in the treatment of and in the improvement of the aesthetic appearance and health of human skin.
It is an object of the invention to provide compositions and methods for treating, ameliorating, inhibiting and/or preventing dermatological signs of aging. It is another object of the invention to provide methods for treating, ameliorating, inhibiting and/or preventing dermatological signs of aging by inducing the expression of thymosin beta-4 in skin cells to improve the appearance of skin. It is a further object of the invention to provide compounds, other than retinoids, that stimulate thymosin beta-4 expression, for a time sufficient to improve the aesthetic appearance of said human skin, and to provide methods for identifying compounds that are useful for treating, ameliorating, inhibiting and/or preventing dermatological signs of aging, by administering agents that stimulate or upregulate expression of thymosin beta-4 in skin cells.
The foregoing discussion is presented solely to provide a better understanding of nature of the problems confronting the art and should not be construed in any way as an admission as to prior art.